Every GLP-1 Medication Ranked: Semaglutide vs Tirzepatide vs Retatrutide vs Liraglutide

GLP-1 is now a broad category. When the media talks about "the weight loss drug," they're usually talking about semaglutide (Ozempic/Wegovy) or tirzepatide (Mounjaro/Zepbound). But the class is larger — and growing fast.

Here's every major GLP-1 medication compared honestly, with the data that actually matters.

The Quick Summary

If you want the short version: - Best efficacy: Tirzepatide > Semaglutide > Liraglutide - Best cost (compounded): Semaglutide and tirzepatide are roughly comparable via telehealth - Most convenient: All three are weekly injections except liraglutide (daily) - Best pipeline: Retatrutide and orforglipron are coming and look promising

Now the detail.

1. Tirzepatide (Mounjaro/Zepbound) — The Current Best Performer

Brand names: Mounjaro (type 2 diabetes), Zepbound (weight management) Mechanism: Dual GIP + GLP-1 agonist Dosing: Weekly injection, 2.5mg → 5mg → 10mg → 15mg Clinical results: 20-22% body weight reduction at max dose (SURMOUNT-1 trial) Compounded cost at Marrow: Starting from $299/month

Tirzepatide is the benchmark against which everything else in this category is now measured. The SURMOUNT-1 trial showed an average 22.5% body weight reduction at 72 weeks — substantially higher than any head-to-head comparison with semaglutide.

Why? The dual mechanism. Tirzepatide activates both GLP-1 receptors and GIP (glucose-dependent insulinotropic polypeptide) receptors. GIP activation appears to enhance the GLP-1 effects while potentially reducing GI side effects relative to semaglutide alone at comparable efficacy levels.

The SURMOUNT-5 trial — the first direct head-to-head comparison between tirzepatide and semaglutide — confirmed what the data suggested: tirzepatide produced about 20% greater weight loss than semaglutide at comparable doses over the trial period. The difference was clinically meaningful.

Who it's best for: Anyone prioritizing maximum weight loss results. The superior efficacy is well-established.

Downsides: Slightly higher cost in some cases. Availability and compounding legal landscape has evolved — work with a provider who knows the current status.

2. Semaglutide (Ozempic/Wegovy) — The Established Standard

Brand names: Ozempic (type 2 diabetes), Wegovy (weight management), Rybelsus (oral tablet for diabetes) Mechanism: GLP-1 agonist Dosing: Weekly injection, 0.25mg → 0.5mg → 1.0mg → 1.7mg → 2.4mg Clinical results: 15-17% body weight reduction at 2.4mg (STEP-1 trial) Compounded cost at Marrow: Starting from $249/month

Semaglutide is the most-studied GLP-1 medication for weight management and the one with the most real-world data. The STEP trial program enrolled over 4,000 patients and demonstrated consistent 15-17% weight reduction at the highest dose over 68 weeks — results that were unprecedented for a pharmacological weight loss intervention at the time.

Beyond weight loss, semaglutide has the strongest cardiovascular evidence in the class. The SELECT trial (17,604 patients, no diabetes) showed a 20% reduction in major adverse cardiovascular events — heart attacks, strokes, cardiovascular death — in people with established cardiovascular disease. This isn't a weight-loss effect; it's a direct cardioprotective effect from GLP-1 activation.

The FLOW trial extended the evidence base to kidney protection, showing semaglutide significantly reduced progression of chronic kidney disease independent of its metabolic effects.

Who it's best for: People with cardiovascular history who want the strongest CVD evidence, those seeking proven long-term data, and those for whom tirzepatide isn't accessible or appropriate.

Downsides: Lower efficacy ceiling than tirzepatide at equivalent real-world doses.

3. Liraglutide (Saxenda/Victoza) — The Original, Now Largely Superseded

Brand names: Victoza (type 2 diabetes), Saxenda (weight management) Mechanism: GLP-1 agonist Dosing: Daily injection, up to 3.0mg Clinical results: 5-8% body weight reduction (SCALE trial) Cost: Higher than compounded weekly options for similar or worse efficacy

Liraglutide was the first GLP-1 medication approved specifically for weight management (2014). It paved the way for the entire modern GLP-1 era and proved the concept worked.

By current standards, it's no longer competitive. Lower efficacy, daily injection (vs weekly), more injection site reactions, and higher cost than compounded weekly alternatives make it difficult to justify as a first-line choice when semaglutide and tirzepatide are available.

The exception: some patients on liraglutide who've been stable on it for years may have no reason to switch. If it ain't broke, as they say.

Who it's best for: Not many people starting fresh in 2026. If you have a specific reason your physician recommends it, there are valid clinical scenarios — but for most people, semaglutide or tirzepatide is the better choice.

4. Retatrutide — The Pipeline Option to Watch

Brand name: Not yet approved Mechanism: Triple GIP + GLP-1 + Glucagon agonist Dosing: Weekly injection (Phase 3 trials ongoing) Clinical results: ~24% body weight reduction at 12mg in Phase 2 Availability: Not approved; not available via telehealth as of 2026

Retatrutide adds glucagon receptor agonism to the GIP/GLP-1 dual mechanism. Glucagon activation increases energy expenditure — essentially telling your liver and fat tissue to burn more fuel. In Phase 2 trials, retatrutide at the highest dose produced approximately 24.2% body weight reduction over 48 weeks, which would make it the most effective pharmacological weight loss agent to reach Phase 3.

Phase 3 trials are underway. If those data hold, retatrutide will likely be approved in 2026-2027 and will immediately become the efficacy benchmark.

Who it's for: Right now, nobody outside clinical trials. But it's worth understanding as the next evolution of the class.

5. Orforglipron — The Oral Option

Brand name: Not yet approved Mechanism: GLP-1 agonist (oral small molecule) Dosing: Once daily oral pill Clinical results: 9-14% body weight reduction in trials (dose-dependent) Availability: Not approved; expected 2026+

Every GLP-1 so far requires injection. Orforglipron is a small-molecule oral GLP-1 agonist — meaning a daily pill, not a weekly injection. This is potentially the largest market access unlock in the category's history.

The tradeoff: efficacy appears to be closer to liraglutide (~9-14%) than to weekly semaglutide (15-17%). But for the significant population who won't inject, an oral option with meaningful efficacy changes the access equation entirely.

Eli Lilly submitted orforglipron for FDA approval in early 2025. Expected approval and launch in 2026.

Head-to-Head: What the Data Actually Shows

| Medication | Mechanism | Dosing | Avg Weight Loss | Compounded? | |-----------|-----------|--------|-----------------|-------------| | Tirzepatide | GIP+GLP-1 | Weekly | ~20-22% | Yes | | Semaglutide | GLP-1 | Weekly | ~15-17% | Yes | | Retatrutide | GIP+GLP-1+GCG | Weekly | ~24% (Ph2) | No (not approved) | | Liraglutide | GLP-1 | Daily | ~5-8% | Rarely | | Orforglipron | GLP-1 | Daily oral | ~9-14% | No (not approved) |

How to Choose

For maximum weight loss: Tirzepatide. The head-to-head data with semaglutide is clear, and the dual mechanism appears to produce meaningfully better results for most patients.

For established cardiovascular protection: Semaglutide. The SELECT trial data is the most robust in the class for CVD outcomes.

For cost sensitivity: Semaglutide and tirzepatide via compounding are comparably priced at reputable telehealth providers. The cost argument used to favor semaglutide; that gap has largely closed.

For needle phobia: Wait for orforglipron, or try semaglutide first — many people who were nervous about injections find the weekly subcutaneous injection easy to manage.

For athletes and lean patients: Microdosing semaglutide or tirzepatide. The metabolic optimization benefits exist at sub-therapeutic doses without the dramatic appetite suppression.

At Marrow, we prescribe both semaglutide and tirzepatide and can help you determine which is right for your situation. [Start here](/start).